The overall objective of the proposed research is to gain an understanding of the molecular events which underlie processes involved in learning and memory. One model used to study such processes is long-term potentiation (LTP), a type of induced plasticity where the efficacy of synapses is enhanced in a fashion similar to that which occurs during some forms of learning. Recent evidence suggests that GAP-43, an axonally transported phosphoprotein whose synthesis and transport is specifically enhanced during nerve growth and regeneration, may play an important role in LTP. Another model used to study synaptic plasticity is reactive synaptogensis, where normal axons grow and reinnervate denervated areas. In the proposed studies. quantitative electrophoretic and EM, subcellular fractionation. in vitro and in situ hybridization methods, will be used to determine if GAP-43 phosphorylation is correlated with axon growth and/or release of neurotransmitter during LTP, and if GAP-43 plays a role in the growth of axons which occurs during reactive synaptogenesis in the rat hippocampal formation. These studies promise to provide important information regarding the molecular events which occur during synaptic plasticity and may contribute to our understanding of the role played by protein phosphorylation in processes underlying learning and memory.